Reduced expression of p63 has prognostic implications for patients with esophageal squamous cell carcinoma

Abstract

The p63 gene is a member of the p53 family that plays a role in cell differentiation, development and carcinogenesis. The relationship between p63 expression and the prognosis of esophageal squamous cell carcinoma (ESCC) remains unknown. The present study examines the clinical impact of p63 in patients with ESCC. Resected specimens from 180 patients with ESCC were immunostained for p63 and p53. After establishing a cut-off value for p63 expression, we statistically examined its clinical impact and relationship to p53 expression. At a 50% cut-off value for p63 expression, the 5-year overall survival was significantly longer in p63-positive (46.4%) than -negative patients (11.1%, p=0.05). Among the 180 ESCC patients, 171 (95.0%) were p63 immunoreactive and only 9 (5.0%) were negative. The correlation between p63 status and clinicopathological parameters was not significant, although p63-negativity tended to correlate with distant metastasis (p=0.06) and clinical stage (p=0.08). Univariate analysis demonstrated significant correlations between patient survival and tumor diameter, depth of invasion, lymphatic invasion, vascular invasion, lymph node metastasis and distant metastasis. The survival of patients who did not express p63 and p53 was obviously unfavorable (p=0.03). Multivariate analysis revealed that only lymph node metastasis was a critical independent prognostic marker for overall survival (p=0.0015). Expression of p63 was not an independent prognostic factor for overall survival in this study (p=0.69). These data suggest that, although a reduced expression of p63 is infrequent, it has a prognostic impact upon patients with ESCC.

Expression Profile of p63 in 127 Patients with Laryngeal Squamous Cell Carcinoma

“…No, there would be no difference in the outcome with this suggested cutoff because in the present study, 96.0% of the cancers had at least 30% of their nuclei immunostained for p63 protein. These results concur with those reported by other reports [6,10,[13][14][15] . Maybe with a grading system with larger intervals and fewer grades, this could represent a change in the outcome.…”

“…Iwata et al [18] examined specifically the immunohistochemical expression of truncated isoforms ( ⌬ Np63) of p63 and demonstrated that there was no prognostic impact of positive expression of these isoforms in epidermoid carcinomas of the lung. On the contrary, various studies suggested that, although uncommon, the reduced expression of p63 has a negative prognostic impact [15] . Massion et al [9] reported a statistically significant association between immunohistochemical hyperexpression of p63 protein and the amplification of the TP63 gene with better survival rates, in patients with epidermoid carcinoma of the lung.…”

“…Maybe with a grading system with larger intervals and fewer grades, this could represent a change in the outcome. For example, Takahashi et al [15] studied 180 patients with esophageal squamous cell carcinoma and just 5% of them had negative immunostaining for p63, with a cutoff that defined positive staining when more than 50% of cells were…”

Increased ΔNp63 expression is predictive of malignant transformation in oral epithelial dysplasia and poor prognosis in oral squamous cell carcinoma

“…Lo Muzio et al and Moergel et al also have found that the high expression of p63 is significantly associated with the poor prognosis (49,52). In contrast, some reports have shown that reduced p63 expression associates with poor prognosis in the head and neck carcinoma (53)(54)(55). Such discrepancies might be due to the monoclonal A4A antibody used in immunohistochemical analyses.…”

“…Several studies on the assessment of correlation between the positive rate of p63 and patient prognosis in head and neck carcinoma have been reported (25,49,(52)(53)(54)(55). Lo Muzio et al and Moergel et al also have found that the high expression of p63 is significantly associated with the poor prognosis (49,52).…”